Research over the past 40 years has been focused on the potential for using microstructures or vesicles derived from natural and synthetic lipids for applications in areas such as encapsulation, controlled release, biosensors, enzyme immobilization, functional protein reincorporation, etc. Upon coming in contact with water, both natural and synthetic lipids self-organize such that polar hydrophilic regions (headgroups) face the aqueous medium while lipophilic portions of the assembly remain away from the aqueous medium. This process instantaneously produces closed, concentric, spherical lipid membranes called vesicles or liposomes, as well as other morphologies.
Lipid vesicles are generally made of materials having a high amphophilic lipid content, for example, surfactants or phospholipids. There are three general types of vesicles: (1) multilamellar vesicles (MLVs), which are onion-like structures having a series of substantially spherical shells formed of lipid bilayers interspersed with aqueous layers and ranging in diameter from about 0.1-4 .mu.m, (2) large unilamellar vesicles (LUVs) which have a lipid bilayer surrounding a large, unstructured aqueous phase and have a diameter of greater than 1 .mu.m, and (3) small unilamellar vesicles (SUVs) which are similar in structure to the LUVs except that their diameters are less than 0.2 .mu.m. MLVs are ideal for sustained release of reactive materials, while SUVs or LUVs are required for producing stimuli responsive carriers. LUVs are most desirable for the encapsulation of large molecules such as enzymes.
A major drawback of conventional vesicles is that they are relatively unstable toward mechanical, chemical and physical perturbations and, therefore, are unsuitable for a large number of potentially important applications. Strategies for improved stability have included the incorporation of proteins, sugars, and cholesterol following the technique used for vesicle or liposome formation; i.e., well dried thin films of lipids and other material, except protein, are hydrated by addition of water or buffer and vortex mixing the mixture; protein is then added to the lipid films in hydrating buffer. However, these incorporation strategies have had only limited success.
Polymerized vesicles appear to offer a superior alternative to conventional vesicles due to the fact that it is possible to: (1) synthesize tailored molecular assemblies, (2) utilize more cost effective materials, (3) establish synthetic routes, and (4) produce bio-compatible and bio-degradable polymers. Polymerized vesicles represent a class of organic polymers that, like cell wall membranes, are capable of accommodating a wide variety of materials on the surface, in the lipophilic region, and in the central cavity. For example, the hollow cavity of a vesicle can be filled with molecules which are useful in release applications. Similarly, the membrane wall interior of a vesicle can be used for accommodating hydrophobic molecules, while the wall exterior can be used for developing strategies for target recognition and enzyme catalysis.
U.S. Pat. No. 4,900,556 to Wheatley et al. discloses preparation of vesicles (liposomes) by mixing phospholipids, such as phosphatidylcholine and phosphatidylglycerol, and cholesterol. Cholesterol is added to increase fluidity and enhance solute entrapment. The patent describes various release mechanisms such as triggering by complexation of lipids with synthetic poly(carboxylic acid) and also poly(alphaethylacrylic acid). 1,2 diretinoyl-sn-glycero-3-phosphatidylcholine, 1-palmitoyl, 2-retinoyl phosphatidylcholine and azobenzene lipid are also used in triggering liposome disruption by 360 nm light. Ion and temperature induced controlled release mechanisms are also disclosed. However, like other prior art methods, the Wheatley et al. patent release mechanisms are inefficient because the lipids utilized in the preparation of vesicles tend to be unstable and are not alone capable of forming vesicles on polymerizing.